Effect of percutaneous ethanol injection for postoperative recurrence of hepatocellular carcinoma in combination with transcatheter arterial embolization

BACKGROUND/AIMS: This study was conducted to clarify the effect of percutaneous ethanol injection (PEI) in combination with transcatheter arterial embolization (TAE) on prolonging the survival time of patients with postoperative recurrence of hepatocellular carcinoma (HCC). MATERIALS AND METHODS: The subjects were 97 consecutive patients (pts) treated for postoperative recurrent HCC between February 1987 and March 1993. Of these, 25 pts received both TAE and PEI and 72 pts received TAE alone. In the TAE & PEI group, treatment was selected according to the indications: 15 pts received TAE for multiple recurrences following PEI, and the other 10 pts received PEI for a new or residual lesion following TAE. Fourteen demographic, pathological, and clinical variables were evaluated to estimate the relative risk of pts treated with TAE & PEI or with TAE alone. RESULTS: The 1-, 3- and 5- year survival rates in the TAE & PEI group were 100%, 73.2% and 27.2%, respectively, and those in the TAE alone group were 88.9%, 30.2% and 5.5%, respectively. Based on multi-variate Cox regression analysis, the relative risk of cancer death in the TAE & PEI group was 0.32 (95% confidence interval, 0.15 to 0.67). CONCLUSION: The combination of TAE and PEI had a positive palliative effect and increased survival time of patients with postoperative recurrent HCC, compared to results obtained by TAE alone.     

Transcatheter arterial embolization of hepatocellular carcinoma using CO2-US

Enhanced ultrasonography under the injection of microbubbles of carbon dioxide into the hepatic artery (CO2-US) contributed to the treatment of hepatocellular carcinoma in the selection of indication of transcatheter arterial embolization (TAE). Judging from the accumulation of the lipiodol after TAE with the combination of lipiodol, TAE was thought to be effective in the tumor which was enhanced by CO2 microbubbles more strongly and the enhancement was prolonged more longer compared to the surrounding parenchyma, even the tumor had no tumor staining on the hepatic angiography. In none of the tumor which had no enhancement, TAE was effective. In most of the tumor with isoenhancement compared with surrounding parenchyma TAE was not effective.     

Cerebral hemodynamic response to CO2 after severe head injury: clinical and prognostic implications

PURPOSE: To evaluate the efficacy and safety of transcatheter oily chemoembolization therapy (TOCE) via the inferior phrenic artery (IPA) in hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Fifty patients with HCC underwent a total of 82 procedures of TOCE of the IPA, as well as of the hepatic artery. In 16 patients, additional extrahepatic collaterals were depicted and were also embolized in 10 patients. TOCE was performed with an emulsion of iodized oil and doxorubicin hydrochloride, and gelatin sponge particle embolization was added in 32 patients. RESULTS: Initial response showed complete or partial remission of the tumor in 31 patients. The cumulative survival rates after combined TOCE of the hepatic artery, IPA, and other extrahepatic arteries were 89% (6 months), 78% (1 year), 46% (2 year), and 30% (3 year), when calculated from the time of IPA chemoembolization. Liver abscess and empyema developed in one case of combined IPA and multiple intercostal artery chemoembolization. There were no serious complications after IPA chemoembolization alone. CONCLUSION: TOCE of the IPA has a potential therapeutic role as a safe adjunct to TOCE of the hepatic artery in the management of HCC supplied by the IPA.     

Group B Streptococcus infections: new forms. New preventive measures]

Three patients with liver metastases receiving transarterial chemotherapy underwent embolization of extrahepatic collaterals to the liver under temporary balloon occlusion of the proper hepatic artery. Enhancement in the liver and tumors was observed at CT arteriography through the right inferior phrenic artery and was accentuated under balloon occlusion in all patients. A Cyanoacrylate-Lipiodol mixture was infused through the right inferior phrenic artery to occlude arterial communications with intrahepatic arteries. Better contrast agent distribution was obtained in all patients after embolization. It is suggested that this procedure can be effective for arterial redistribution against extrahepatic collaterals to the liver.     

Transcatheter arterial chemoembolization in cytoreduction of inoperable hepatocarcinomas

Transcatheter arterial chemoembolization (TAE) is often considered a mean of palliation for inoperable liver carcinomas. A few centers use a sequential treatment (TAE followed by surgery). However the role of TAE in bringing to surgery patients with hepatocarcinomas (HCC) considered inoperable at first diagnosis is debated. We report on the case of a 57 y.o. male diagnosed as having HCC, inoperable because of bilateral location and size. The patient was treated with repeated TAEs and the results were monitored with CT scans. After three TAEs, the main tumor mass volume was reduced 2.2 fold and the patient could undergo surgery; the postoperative period was uneventful, with no clinical signs of liver failure. Our experience leads us to suggest that TAE, further to being an option for palliation, can be a valuable tool to lead to surgery otherwise inoperable HCC patients.     

Repeated arterial embolization of rat livers by degradable microspheres

A transient arrest of arterial blood flow can be accomplished by intra-arterial injection of a new type of degradable microsphere. The effects of single and multiple injections of these microspheres into rat hepatic arteries were studied by measurements of fractional cardiac output distribution and 133Xe washout from the liver before and after embolization. Injection of these microspheres into the hepatic artery caused a significant but transient reduction of the arterial blood flow to the liver. Repetition of the injection several times over several days produced identical effects on each embolization. No signs of hepatic cell damage were detected after repeated embolization, as suggested by assay of the serum enzymes or the Bromsulphalein retention test.     

Zinc metabolism after transcatheter arterial embolization for hepatocellular carcinoma

BACKGROUND/AIMS: Zinc metabolism after transcatheter arterial embolization (TAE) was studied in 15 cases of hepatocellular carcinoma (HCC) with liver cirrhosis (LC). METHODOLOGY: Serum zinc concentrations, 24-hr urinary excretion of zinc, blood ammonia (NH3) and plasma endotoxin (Et) levels were measured before and one, three and seven days after TAE. RESULTS: Serum zinc levels one day after TAE were decreased (p<0.05) as compared to those before TAE and then returned to pretreatment values three days or more after TAE. Urinary excretion of zinc increased (p<0.01) one day after TAE, but then returned to the pretreatment value three days after TAE. Although blood NH3 and plasma Et levels increased (P<0.05) the day after TAE, these parameters recovered on the third day. CONCLUSIONS: Decrease in the serum zinc concentration after TAE is considered to be due to changes in the zinc distribution in the body associated with endotoxemia, as well as increased urinary zinc excretion.     

Nonsurgical management of patients with blunt hepatic injury: efficacy of transcatheter arterial embolization

OBJECTIVE: We evaluated the efficacy of transcatheter arterial embolization (TAE) for patients with blunt hepatic injury. SUBJECTS AND METHODS: Of 372 patients with trauma, 60 had evidence on CT of hepatic injury (Mirvis classification). Six of the 60 patients required emergency laparotomy and were excluded. Of the 54 remaining patients, 28 were classified as having high-grade hepatic injury (Mirvis classification of 3 or 4). All 28 underwent arteriography, and TAE was performed in single or multiple hepatic arterial branches when extravasation was seen. Angiography was repeated and cholescintigraphy was performed on patients with continued bleeding or biloma. RESULTS: Injuries detected were grade 1 (n = 13), grade 2 (n = 13), grade 3 (n = 20), and grade 4 (n = 8). The injury was correlated with the degree of hemoperitoneum seen on CT. Patients with low-grade injuries (Mirvis classification of 1 or 2) were treated conservatively, and no deaths or liver-related morbidity occurred. Of the 28 patients with high-grade injury, 15 also had angiographic evidence of extravasation and underwent TAE. The average fluid resuscitation volume was significantly larger in this group than in the other 13 patients with high-grade injuries who did not undergo TAE. Embolization was successful in all 15 patients, and the shock index was significantly reduced after TAE. All patients survived, with follow-up at 1-8 months (2.5 +/- 1.8 months, mean +/- SD). CONCLUSION: TAE is an effective alternative to surgery for patients with high-grade liver injury.     

The treatment of hemoptysis by embolization of the systemic arteries (author's transl)

The authors present their still limited experience of embolization of systemic arteries as the treatment of hemoptysis. Their cases illustrate the indications, contra-indications, causes of failure and effectiveness of this therapeutic method in pneumology. They had to refuse who patients: in the first, the pathological bronchial artery arose from a common trunk with the intercostal which gave rise to an anterior spinal artery. The second patient showed signs of medullary involvement on injection of a pathological right intercostal artery, which in their opinion is also a contra-indication of embolization, although no anterior spinal artery was demonstrated on the arteriogrammes. Six patients were treated by embolization. In the case of one patient, treatment was a failure owing to incomplete embolization. A main esophageal pedicle supplied a high flow bronchial artery anastomosis. These important collateral esophageal vessels compromize the effectiveness of bronchial embolization.     

A potential pitfall in bronchial artery embolization

Two cases of patients with massive haemoptysis undergoing bronchial arteriography are described. Both had collateral vessels which filled the right subclavian artery from the right intercosto-bronchial trunk. Such vessels form a potential route for the passage of embolic material into the subclavian artery and its branches during therapeutic bronchial artery embolization. To avoid this potential complication, super selective catheterization with the positioning of the catheter tip well into the bronchial artery beyond the origin of the intercostal artery and any large collateral vessels is recommended.     

Hepatocellular carcinoma: CT and MR features after transcatheter arterial embolization and percutaneous ethanol injection

PURPOSE: To investigate the reliability of computed tomography (CT) and magnetic resonance (MR) imaging in the evaluation of the response of hepatocellular carcinoma (HCC) to transcatheter arterial embolization (TAE) followed by percutaneous ethanol injection (PEI). MATERIAL AND METHODS: Between January 1991 and November 1992, 20 patients (15 men and five women, aged 53-73 years [mean, 64.6 years]) with 31 HCC lesions underwent CT and MR imaging before and after treatment with combined TAE and PEI. RESULTS: Twenty-seven tumors, which were hypointense on post-treatment T2-weighted images and on gadolinium-enhanced T1-weighted images, were seen to be necrotic at biopsy. In four cases of incomplete necrosis, viable tumor was hyperintense on T2-weighted images and was enhanced after administration of contrast material. CT provided a larger spectrum of imaging features as a result of the presence of both hyperattenuating areas (caused by retention of iodized oil) and hypoattenuating areas (due to ethanol-induced necrosis). CONCLUSION: CT and MR imaging findings proved useful in the evaluation of the response of HCC to combined TAE and PEI.     

The significance of the occlusion in making dentures

PURPOSE: Multivariate analysis was used to study the effectiveness and optimum dose level of Lipiodol (LP) in transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC). METHODS: A total of 219 cases of nodular type HCC, with a tumor diameter less than 7 cm, were studied. TAE was performed using both Gelfoam sponge (GS) and LP in 158 cases; in the remaining 61 cases only GS was used. RESULTS: Statistical stepwise variable selection revealed that only LP had a negative T-value, suggesting that LP is a useful factor for prognosis. The most favorable effect on patient prognosis was obtained with an LP dose level (expressed in mm) of 1-1.5 times the absolute value of the tumor diameter (expressed in cm). CONCLUSION: A significant difference (p < 0.01, log-rank test) in survival was found between the GS with LP group and the GS only group, using Cox's proportional hazard model.     

Transcatheter arterial renal and adrenal embolization with iohexol-ethanol solutions. Animal experimental study and clinical application

RATIONALE AND OBJECTIVES: The authors compared the embolic effect of radiolucent absolute ethanol (AE) with that of a radiopaque iohexol-ethanol (IES) solution for renal ablation in dogs and for the destruction of human aldosteronomas by the technique of transcatheter arterial embolization (TAE) to test whether IES can be an alternative to AE. METHODS: The embolic agents were infused through a balloon catheter into the renal arteries of 17 dogs (9 infused with 0.3 mL/kg AE; 8 infused with IES). The immediate and parenchyma were compared between the two groups. Transcatheter arterial embolization with IES also was performed in three humans with unilateral aldosteronoma. RESULTS: The IES was visualized faintly under fluoroscopy in all dogs. There were no significant differences in embolic effects between the AE and IES. Three patients with aldosteronoma were treated successfully by TAE with IES. CONCLUSIONS: The IES can be used as a "visible ethanol" to improve the safety and ease of ethanol embolization.     

Resection for extrahepatic recurrence of hepatocellular carcinoma

A total of 277 patients with hepatocellular carcinoma (HCC) underwent hepatic resection over a 20-year period. Twelve of 36 patients with recurrence confined to extrahepatic organs underwent surgical resection. There were no complications but one patient died in hospital from secondary intrahepatic recurrence. The 1-, 2- and 5-year survival rates for these 12 patients after hepatic resection were 92, 52 and 26 per cent respectively and were better than those of 24 patients who did not undergo resection for recurrence. The mean survival following resection for recurrent disease was 19.7 months and the longest survival time was nearly 8 years. Secondary recurrence after resection of metastases developed more commonly in the liver than in extrahepatic organs. Among the eight patients who survived for more than 4 months after the second operation, secondary recurrence developed in the liver and extrahepatic organs in eight and four patients respectively. In selected patients with isolated extrahepatic recurrence of HCC, surgery is effective in controlling extrahepatic disease and offers the only chance of long-term survival.     

Diminution of the number of gamma delta T lymphocytes in hepatocellular carcinoma patients treated with transcatheter arterial embolization

gamma delta T lymphocytes, which are CD3+ lymphocytes that express gamma delta chains of the T-cell antigen receptor (TCR) on their surface, are functionally distinct from alpha beta T lymphocytes, which express alpha beta chains of the TCR. gamma delta T lymphocytes are thought to differentiate in mouse hepatic sinusoids, to play a role in antitumor action, and to act as natural killer cells. The purpose of this study was to examine whether gamma delta T lymphocytes in the peripheral blood are suppressed when hepatic sinusoids are damaged during transcatheter arterial embolization (TAE). The numbers of alpha beta T lymphocytes and gamma delta T lymphocytes in the peripheral blood were examined with monoclonal antibodies and flow cytometry before and after TAE in 32 patients (from 46 to 78 years of age) with liver cirrhosis and hepatocellular carcinoma. The number of alpha beta T lymphocytes before and after TAE was unchanged. However, the number of gamma delta T lymphocytes and the ratio of gamma delta T lymphocytes to CD3+ lymphocytes were significantly decreased for 3 weeks after TAE treatment. This decrease suggests that TAE suppresses the supply of gamma delta T lymphocytes to the peripheral blood. In addition, TAE may weaken a patient's antitumor immunity, because gamma delta T lymphocytes that have antitumor activity decrease after TAE.     

Hepatic arterial infusion chemotherapy (HAI) for advanced hepatocellular carcinoma inefficacious with transcatheter arterial embolization (TAE)

For 6 patients with advanced hepatocellular carcinoma (HCC) in whom TAE was inefficacious, we tried hepatic arterial infusion chemotherapy. 5-FU 500 mg/day + CDDP 10 mg/day was administered during 5 days. The AFP level was decreased for 4 patients, and 2 patients showed a partial response in CT image. These 2 patients have been alive over 22 and 18 months, respectively. These results suggest that 5-FU + CDDP HAI might be a useful treatment of HCC inefficacious with TAE.     

Ruptured hepatocellular carcinoma: treatment strategy and prognostic factor analysis

BACKGROUND: The prognosis of ruptured hepatocellular carcinoma (HCC) is generally poor, but few studies have focused on the analysis of prognostic factors of this catastrophic event. METHODS: Eighty-four consecutive patients with ruptured HCC were included. Twenty-nine clinical and laboratory variables were correlated to prognosis by using uni- and multivariate analyses. RESULTS: Epigastralgia and/or right upper quadrant abdominal pain was the most common initial presentation (70%), followed by shock (42%), abdominal distension (27%) and others (17%). Of these 84 patients, 50 patients were treated by supportive measure, 21 by operation and 13 by transcatheter arterial embolization (TAE). The median survival was 13, 30 and 202 days in each group, respectively, and 24 days overall. TAE showed the lowest hemostatic failure rate (20%). Univariate analysis showed that active treatment (operation or TAE), group I tumor with a solitary nodule or single nodule with proliferation into surrounding area, serum creatinine (< or = 1.2 mg/ml), alkaline phosphatase (< or = 95 U/L), alanine aminotransferase (ALT, < or = 40 U/L), total bilirubin (< or = 1.6 mg/ml), initial systolic blood pressure (> or = 90 mmHg), and absence of main portal vein thrombosis were correlated with a survival longer than 90 days (p < 0.05) in univariate analysis. Active treatment, ALT level and initial systolic blood pressure were still significant in multivariate analysis (p < 0.05). CONCLUSIONS: TAE may help stop the tumor bleeding. Treatment regimen, ALT levels and initial blood pressure are correlated with the prognosis of ruptured HCC.     

Subsegmentectomy or segmentectomy in hepatocellular carcinoma

BACKGROUND/AIMS: We determined the optimal therapeutic strategy for improving survival in patients with hepatocellular carcinoma (HCC), based on an analysis of our surgical results. METHODOLOGY: Between January 1990 and December 1996, 205 patients underwent initial curative hepatectomy. The liver volume to be resected was decided according to the plasma retention of indocyanine green 15 minutes after injection. The appropriate subsegmental and segmental areas were disclosed by staining under ultrasonographic guidance. Limited resection or tumor enucleation was performed in 119 patients, subsegmentectomy or segmentectomy in 71, and lobectomy or extended lobectomy in 15. RESULTS: Intrahepatic recurrence was documented in 115 patients, 46 of whom died from cancer recurrence. Disease free survival was 65% after 1 year, 35.1% after 3 years and 25.3% after 5 years. The type of hepatectomy (limited vs. subsegmental or segmental resection) significantly affected the cumulative survival (p = 0.047) and disease free survival rates (p < 0.01). Among the 115 patients with recurrence, 22 patients underwent repeated hepatectomy combined with TAE (transcatheter arterial embolization) and the remainder underwent TAE alone. Patients who underwent repeated hepatectomy combined with TAE survived significantly longer after recurrence than those who underwent TAE alone (p = 0.0197). CONCLUSION: Initial subsegmentectomy or segmentectomy prolongs disease free survival, and patients eligible for repeated hepatectomy combined with TAE after recurrence have a good chance of long-term survival. Subsegementectomy or segmentectomy should be performed in a lot more HCC patients in order to improve survival.     

The relationship between hepatoma and portal vein

Hepatic cells receive dual blood supply of the arterial and portal systems, but hepatoma has been thought to be supplied completely by hepatic artery. However, transcatheter hepatic artery embolization (TAE) has not been able to damage hepatoma entirely. For the study on the relationship between hepatoma and portal vein, I gave intraportal infusions of bromodeoxyuridine. (BrdU), an analogue of thymidine, to 10 patients with hepatoma at the time of surgery, and counted BrdU-positive nuclei immunohistochemically using the anti-BrdU monoclonal antibody. The labeling index, or percentage of BrdU-labelled cells, was 2.0 +/- 1.1% (mean +/- SD) in the cases without TAE and 11.9 +/- 4.2% in the other after TAE. On the other hand, examining the specimens with Microfil injected into the portal branch showed the distribution of portal branches in the hepatoma by radiograph or microscope. It is concluded that hepatoma does not receive arterial blood supply alone but the portal vein participates in vascular distribution of hepatoma, and the participation gets larger after TAE. It is suggested that this finding could be of great importance in planing treatment of patients with hepatoma.     

The safety and efficacy of transcatheter arterial chemoembolization in the treatment of patients with hepatocellular carcinoma and main portal vein obstruction. A prospective controlled study

BACKGROUND: Transcatheter arterial chemoembolization (TACE) has been contra-indicated for the treatment of patients with hepatocellular carcinoma (HCC) and main portal vein (MPV) obstruction because of the potential risk of hepatic insufficiency resulting from ischemia after TACE. The current controlled study was undertaken to assess the safety, efficacy, and predictive factors of favorable response to TACE in patients with HCC and MPV obstruction with good hepatic function and adequate collateral circulation around the MPV. METHODS: Of a total of 47 patients, 31 were treated with TACE, and 16 who declined the procedures were untreated controls. Thirty-six patients (77%) had diffuse-type HCC and 11 (23%) had nodular-type HCC. During the first week after TACE immediate postprocedural complications were evaluated, and the development of hepatic insufficiency as a late complication was assessed at the end of the fourth week. The cumulative survival rate was estimated by the Kaplan-Meier method, and predictors of better prognosis were obtained by univariate and multivariate analyses. RESULTS: Although no patients showed clinical evidence of hepatic insufficiency as an immediate complication, transient fever and abdominal pain were common. Progressive hepatic insufficiency developed at the fourth week; however, there was no difference between the treated and untreated groups. The survival time of treated patients was statistically no longer than that of untreated patients. In the univariate analysis, tumor type and size, the pattern of iodized oil uptake in the tumor, and the presence of iodized oil uptake in the tumor thrombi at the MPV significantly influenced the prognosis. Tumor type, whether treated or not, was the most important prognostic factor patients with nodular-type HCC had significantly longer survival time (median, 11 months) than those with diffuse-type HCC (median, 4 months). Regarding the efficacy of TACE, there was no statistical difference in survival between treated and untreated diffuse-type HCC patients. In comparison, with nodular-type HCC it seemed that survival time was longer for TACE-treated patients (median, 30 months) than for untreated patients (median, 7 months). CONCLUSIONS: TACE may be a safe modality for the treatment of patients with HCC and MPV obstruction, provided that the patients have good hepatic function and collateral circulation around the MPV. However, TACE was not efficacious in the treatment of diffuse-type HCC. The authors recommend TACE for treating nodular-type HCC because of the potential benefit of prolonged survival.